Lipopolysaccharide-induced expression of multiple alternatively spliced MEFV transcripts in human synovial fibroblasts: a prominent splice isoform lacks the C-terminal domain that is highly mutated in familial Mediterranean fever.

摘要: Objective To investigate the expression of familial Mediterranean fever (FMF) gene (MEFV) in human synovial fibroblasts. Methods MEFV messenger RNA fibroblasts, chondrocytes, and peripheral blood leukocytes (PBLs) was analyzed by semiquantitative real-time polymerase chain reaction ribonuclease protection assay. The subcellular localization pyrin, MEFV product, determined transfected fibroblasts HeLa cells with plasmids encoding pyrin isoforms. Native detected an antipyrin antibody. Results MEFV expressed but not chondrocytes. Four alternatively spliced transcripts were identified: extension exon 8 (exon 8ext) resulting a frameshift that predicts truncated protein lacking exons 9 10, addition 4a) predicting at 5, in-frame substitution 2a for 2, previously described removal 2 2Δ). Exon 8ext represented 27% total message population fibroblasts. All other rare. Consensus induced lipopolysaccharide PBLs. In cells, proteins encoded all highly splice forms cytoplasmic. contrast, native predominantly nuclear neutrophils, dendritic cytoplasmic monocytes. Conclusion Several are inducible A prominent isoform lacks C-terminal domain contains majority mutations found patients FMF. While recombinant major isoforms cytoplasmic, is several cell types. Thus, mechanisms to splicing patterns must control pyrin's distribution.